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Biomedical subjects

M F Saad

Publications and source records attributed to M F Saad.

At least 73 records · Page 4Linked to original sources
PubMed1991

Insulin resistance associated with lower rates of weight gain in Pima Indians.

UNLABELLED: Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD). RESULTS: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P less than 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally-(r = 0.19, P less than 0.01) and maximally-stimulating (r = 0.34, P less than 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians.

Adolescent↗
PubMed1991

Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians.

Pima Indians have the highest reported prevalence rate of noninsulin-dependent diabetes mellitus (NIDDM) in the world, so that metabolic comparisons with caucasians, who have a much lower rate, should provide insights into the pathogenesis of NIDDM. We have compared 81 caucasians with 211 Pima Indian nondiabetic subjects similar in age, sex, degree of obesity, and glucose tolerance. During a hyperinsulinemic euglycemic clamp at physiological insulin concentrations, Pima Indians were 17% more insulin resistant than caucasians after accounting for any differences in degree of obesity (P less than 0.0001). During oral glucose tolerance testing, mean plasma insulin concentrations were 33% higher in the Pimas (P less than 0.0001), but these differences were largely explained by the greater insulin resistance in the Pimas. Insulin clearance did not differ between the races. However, early insulin responses were exaggerated in the Indians and not explained by insulin resistance. After accounting for differences in insulin action, plasma insulin concentrations in Pima Indians were 50% higher than those in caucasians 3-5 min after iv glucose (P less than 0.0001), 38% higher 10 min after the end of a meal (P less than 0.0001), and 20% higher 30 min after an oral glucose load (P less than 0.006). These data suggest that in addition to insulin resistance, Pima Indians have exaggerated early insulin release and either increased beta-cell mass or enhanced beta-cell sensitivity to glucose. The data argue against low or delayed insulin secretion as primary factors leading to NIDDM in Pima Indians and favor insulin resistance as the underlying and initiating cause of the disease.

Administration, Oral↗
PubMed1991

Abnormal glucose tolerance during pregnancy in Pima Indian women. Long-term effects on offspring.

The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima Indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 162). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation.

Adolescent↗
PubMed1991

Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens.

The ability of an albumin-to-creatinine ratio, measured in a single untimed urine specimen, to indicate the likelihood of developing overt diabetic nephropathy was determined in 439 Pima Indians (134 men, 305 women) aged 25 years or older with non-insulin-dependent diabetes. During a mean follow-up period of 4.2 years, 59 (13%) of the subjects developed overt nephropathy, 47 (80%) of whom had albumin-to-creatinine ratios of 30 mg/g or greater at baseline. Subjects with albumin-to-creatinine ratios of 30 to 299 mg/g (a level of excretion often termed "microalbuminuria") had 9.2 times (95% confidence interval, 4.4 to 21.4) the incidence of overt nephropathy of those with ratios of less than 30 mg/g. Furthermore, the albumin-to-creatinine ratio remained a strong predictor of overt nephropathy even when controlled for age, sex, diabetes duration, mean blood pressure, and 2-hour postload plasma glucose concentration with a proportional-hazards function analysis. Thus, an albumin-to-creatinine ratio measured in a single untimed urine specimen is an effective means of identifying diabetic subjects who are at risk of developing overt nephropathy that could replace the more traditional timed urine collections.

Adult↗
PubMed1991

A two-step model for development of non-insulin-dependent diabetes.

Both insulin resistance and beta-cell dysfunction occur during the development of non-insulin-dependent diabetes mellitus (NIDDM), but controversy exists about which lesion is primary. Based on longitudinal studies in the Pima Indians, a population with the world's highest reported prevalence of NIDDM, a two-step model for development of the disease is proposed. The first step is transition from normal to impaired glucose tolerance, for which insulin resistance is the main determinant, and the second and later step is worsening from impaired glucose tolerance to diabetes, in which beta-cell dysfunction plays a critical role. This hypothesis is consistent with findings from other ethnic groups from many parts of the world.

Adolescent↗
PubMed1990

Islet amyloid polypeptide in diabetic and non-diabetic Pima Indians.

Islet amyloid may have a pathological role in the development of Type 2 (non-insulin-dependent) diabetes mellitus. The prevalence of islet amyloid has been investigated on post-mortem pancreatic tissue from both diabetic and non-diabetic Pima Indian subjects who had previously been assessed by oral glucose tolerance tests. Islets were examined for amyloid deposits and for cellular immunoreactivity to pancreatic hormones and islet amyloid polypeptide, the constituent peptide of islet amyloid. Twenty of 26 diabetic subjects (77%) had islet amyloid, compared with one of 14 non-diabetic subjects (7%). Twelve of the diabetic subjects (46%) had amyloid in more than 10% of their islets, whereas only 4% of islets were affected in a single non-diabetic subject. Positive immunoreactivity for islet amyloid peptide was present in the islet amyloid and in islet cells in 54% of the diabetic and 50% of the non-diabetic subjects. Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia.

Aged↗
PubMed1990

Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus.

We studied the occurrence of renal disease by measuring serum creatinine and urine protein concentrations in the diabetic members of 316 Pima Indian families with Type 2 (non-insulin-dependent) diabetes in two successive generations to determine if diabetic renal disease aggregates in families. After adjustment for sex and other risk factors, proteinuria occurred among 14.3% of the diabetic offspring if neither parent had proteinuria, 22.9% if at least one diabetic parent had proteinuria, and 45.9% if both parents had diabetes and proteinuria. Among male offspring, an elevated serum creatinine concentration (greater than or equal to 177 mumol/l) was present in 11.7% if the parent had an elevated creatinine and in 1.5% if the parent did not. Thus, proteinuria and high serum creatinine aggregated in diabetic families, suggesting that susceptibility to renal disease is inherited independently of diabetes.

Adult↗
PubMed1990

Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ.

Reduced oxidation of fat leading to a positive fat balance could be a factor in the development of obesity. Twenty-four-hour respiratory quotient (RQ) was measured in 152 nondiabetic Pima Indians fed a weight-maintenance diet [87 males and 65 females; 27 +/- 6 yr (mean +/- SD); 93.9 +/- 22.9 kg; 32 +/- 9% fat]. Twenty-four-hour RQ varied from 0.799 to 0.903. Prior change in body weight, 24-h energy balance, sex, and percent body fat explained 18% of the variance in 24-h RQ (P less than 0.001). In a subgroup of 66 siblings from 28 families, family membership explained 28% of the remaining variance in 24-h RQ (P less than 0.05). In 111 subjects for whom follow-up data (25 +/- 11 mo) were available, 24-h RQ was correlated with subsequent changes in body weight and fat mass (r = 0.27, P less than 0.01 and r = 0.19, P less than 0.05, respectively). Subjects with higher 24-h RQ (90th percentile) independent of 24-h energy expenditure were at 2.5 times higher risk of gaining greater than or equal to 5 kg body weight than those with lower 24-h RQ (10th percentile). We conclude that in Pima Indians fed a standard diet 1) family membership is the principal determinant of the ratio of fat to carbohydrate oxidation, and 2) a low ratio of fat to carbohydrate oxidation is associated with subsequent weight gain independent of low energy expenditure and may contribute to the familial aggregation of obesity.

Adult↗
PubMed1990

Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes.

The incidence of fatal coronary heart disease (CHD) was determined in a population of Pima Indians from the Gila River Indian Community in Arizona. Between 1975 and 1984, 394 deaths occurred among 4,828 subjects aged 5 years or older, and 199 of these occurred in the 1,093 persons with non-insulin-dependent diabetes. Only 28 deaths were attributed to CHD; all occurred among the 689 diabetic persons 45 years of age or older. No CHD deaths occurred among the 419 nondiabetic subjects 45 years of age or older. The rate of fatal CHD among the diabetic subjects was higher in men than in women and increased with advancing age and duration of diabetes. A higher incidence of fatal CHD was associated with proteinuria, renal insufficiency, medial arterial calcification, diabetic retinopathy, insulin therapy, and an abnormal electrocardiogram. In Pima Indians aged 50-79 years, the incidence of fatal CHD was less than half that found in the Framingham population after controlling for age, sex, and diabetes (incidence rate ratio, 0.4; 95% confidence interval, 0.2-0.7). Factors protecting Pima Indians from fatal CHD may include racial heritage, low serum concentrations of total and low density lipoprotein cholesterol, and rarity of heavy smoking. Among the diabetic subjects, mortality from diabetic renal disease, which shows many of the same risk factors, may selectively compete and remove those at risk for fatal CHD. This would not, however, explain the lack of fatal CHD among the nondiabetic subjects. Fatal CHD shares many of the risk factors associated with the specific microvascular complications of diabetes, and diabetes and its associated attributes are the major predictors of fatal CHD in this population.

Aged↗
PubMed1990

Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus.

Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules.

Adolescent↗
PubMed1990

Periodontal disease and NIDDM in Pima Indians.

The goal of this study was to determine the prevalence and incidence of periodontal disease and its relationship with non-insulin-dependent diabetes mellitus (NIDDM). Two thousand two hundred seventy-three Pima Indians (949 men, 1324 women) aged greater than or equal to 15 yr from the Gila River Indian Community in Arizona were examined between 1983 and 1989. Periodontal disease was diagnosed by tooth loss and by percentage of interproximal crestal alveolar bone loss ascertained from panoramic radiography. Subjects with little or no evidence of periodontal disease were classified as nondiseased. Thus, the incidence of advanced periodontal disease was determined. The age- and sex-adjusted prevalence of periodontal disease at first dental examination was 60% in subjects with NIDDM and 36% in those without. Twenty-two new cases developed in a subset of 701 subjects (272 men, 429 women) aged 15-54 yr who initially had little or no evidence of periodontal disease and had at least one additional dental examination. The incidence of periodontal disease in this group was similar in men and women (incidence-rate ratio 1.0, 95% confidence interval [Cl] 0.5-1.9, controlled for age and diabetes). Higher age predicted a greater incidence of periodontal disease (chi 2 = 30.6, df = 3, P less than 0.001, controlled for sex and diabetes). The rate of periodontal disease in subjects with diabetes was 2.6 times (95% Cl 1.0-6.6, controlled for age and sex) that observed in those without. Although periodontal disease was common in nondiabetic Pima Indians, in whom most of the incident cases occurred, diabetes clearly conferred a substantially increased risk. Thus, periodontal disease should be considered a nonspecific complication of NIDDM.

Adolescent↗
PubMed1990

Insulin and hypertension. Relationship to obesity and glucose intolerance in Pima Indians.

The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2873 Pima Indians aged 18-92 yr (mean 37 yr). Age- and sex-adjusted to the Pima population, the prevalence of hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg, or receiving drug treatment) was 7.1% for subjects with normal glucose tolerance compared with 13.0% for subjects with impaired glucose tolerance (IGT) and 19.8% for those with non-insulin-dependent diabetes mellitus (NIDDM) (P less than 0.001). The prevalence ratio of hypertension was 1.8 (95% confidence interval [CI] 1.2-2.5) for IGT and 2.6 (95% CI 2.0-3.2) for NIDDM compared with normal glucose tolerance, controlled for age, sex, and body mass index (BMI). In logistic regression analysis, hypertension was positively related to age, male sex, BMI, glucose tolerance, and fasting but not 2-h postload serum insulin concentration. Among subjects not taking antihypertensive drugs, however, neither fasting nor 2-h postload serum insulin was significantly related to hypertension. Furthermore, in 2033 subjects receiving neither antihypertensive nor antidiabetic drugs, blood pressure was not significantly correlated to fasting insulin concentration, and 2-h postload serum insulin was negatively correlated with diastolic blood pressure. In conclusion, insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians.

Adolescent↗
PubMed1989

Sequential changes in serum insulin concentration during development of non-insulin-dependent diabetes.

Changes in serum insulin concentrations during deterioration of glucose tolerance were studied in 81 Pima Indians who worsened from normal to impaired glucose tolerance (IGT); 44 who changed from IGT to non-insulin-dependent diabetes mellitus (NIDDM); 27 who were seen at diagnosis of NIDDM and 1.4-8.5 years later; and 11 subjects who were seen at each of these stages. When their glucose tolerance was normal, subjects who later developed NIDDM had higher fasting and post-load insulin concentrations than controls of similar age and body mass index who did not become diabetic. Onset of IGT or NIDDM was associated with a further increase in fasting insulin concentrations, although a deterioration from IGT to NIDDM was associated with little change in insulin responses to oral glucose in spite of increased blood glucose. After the onset of NIDDM, both fasting and post-load insulin concentrations diminished. These longitudinal data show that, as glucose tolerance worsens, insulin and glucose concentrations in individuals follow the inverted-U-shaped relation previously reported in cross-sectional population studies.

Adolescent↗
PubMed1989

Albuminuria in type 2 (non-insulin-dependent) diabetes mellitus and impaired glucose tolerance in Pima Indians.

The prevalence of abnormal urinary albumin excretion, defined by a urine albumin to creatinine ratio greater than or equal to 30 mg/g (approximately equivalent to an albumin excretion rate of greater than or equal to 30 mg/24 h), was determined in 2728 Pima Indians aged greater than or equal to 15 years from the Gila River Indian Community in Arizona, a population with a high prevalence of Type 2 (non-insulin-dependent) diabetes mellitus. Excessive albumin excretion was present in 8% of subjects with normal glucose tolerance, 15% of those with impaired glucose tolerance, and 47% of subjects with diabetes. The intermediate prevalence of abnormal albuminuria in those with impaired glucose tolerance suggests that hyperglycaemia even at levels below those diagnostic of diabetes is associated with renal abnormalities in some subjects and that these abnormalities may precede the onset of diabetes. Abnormal albuminuria at levels not reliably detected by the usual dipstick methods was commonly observed in Pima Indians with diabetes, even those with diabetes of recent onset. Associations were found with age, duration of diabetes, level of glycaemia, blood pressure, and treatment with insulin.

Adult↗
PubMed1988

The natural history of impaired glucose tolerance in the Pima Indians.

Among 384 Pima Indians with impaired glucose tolerance according to World Health Organization criteria who were followed for 1.6 to 11.5 years (median, 3.3), non-insulin-dependent diabetes mellitus (NIDDM) developed in 118 (31 percent), glucose tolerance remained impaired in 100 (26 percent), and glucose tolerance returned to normal in 166 (43 percent). The cumulative incidence of NIDDM was 25 and 61 percent at 5 and 10 years, respectively. The risk of development of diabetes was 6.3 times (95 percent confidence interval, 3.8 to 10.6) as high as in a normoglycemic control group (n = 752). Variables predicting deterioration to NIDDM were age up to the age of 40, after which increasing age had a beneficial effect; higher plasma glucose levels during fasting and after carbohydrate loading; and higher serum insulin levels after fasting and lower levels after carbohydrate loading, suggesting that insulin resistance and decreased beta-cell responsiveness are important determinants of the clinical outcome of impaired glucose tolerance. Obese subjects had 2.9 times (95 percent confidence interval, 2.0 to 10.9) the incidence of NIDDM as the nonobese. Obesity was not, however, predictive of progression to NIDDM after an adjustment for plasma glucose and serum insulin levels. We conclude that in this population approximately one fourth of subjects with impaired glucose tolerance have NIDDM at five years and two thirds at 10 years (approximately one third revert to normal) and that age and plasma glucose and insulin levels are the best predictors of clinical outcome.

Adult↗
PubMed1988

Transient impaired glucose tolerance in Pima Indians: is it important?

As part of a continuing epidemiological study of non-insulin dependent diabetes among Pima Indians 154 subjects who had had a transient impairment of glucose tolerance were followed up for 1.2-16.9 (median 5.8) years after their glucose tolerance had returned to normal. Of these, 49 subsequently developed diabetes; 26 subsequently developed impaired glucose tolerance; and 79 had normal glucose tolerance at the last examination. The cumulative incidence of diabetes was 16% and 48% at five and 10 years of follow up respectively, compared with 3% and 8% for a control group of 1245 members of the same population. After adjustment for age, sex, body mass index, and plasma glucose concentration two hours after glucose loading the incidence of diabetes among the subjects who had had transient impaired glucose tolerance was 3.0 times that among the controls (95% confidence interval 2.1 to 4.3). Proportional hazards function analysis indicated that obesity was the most important predictor of subsequent development of diabetes. The results suggest that transient impairment of glucose tolerance indicates, at least in some subjects, a predisposition to diabetes and should not be considered clinically unimportant.

Age Factors↗